The objective of the proposed research is to increase our understanding of a rarely reported disorder characterized by decreased leukocyte myeloperoxidase (MPO) activity. This should provide increased knowledge of normal and abnormal leukocyte physiology. With the use of an automated leukocyte differential counter which incorporates MPO stains, we have identified eight probands during the past two years. Four of these are members of large families providing the opportunity to study large numbers of MPO deficient subjects. Investigations to determine the clinical significance of the deficiency include: history and physical examination, infectious disease questionnaire, and prospective evaluation of infectious episodes. A genetic analysis of each family is being done. MPO will be isolated and purified for characterization to determine whether there is a deficiency of qualitatively normal enzyme or an abnormal enzyme present with reduced activity.